The control of acid-base regulation by the kidney is critical in maintaining body electrolyte homeostasis. Many areas of the nephron participate in this control but little is known about the factors which affect collecting duct acidification. This nephron site is of critical importance since it is the location where the steepest pH gradients are set, where bicarbonate absorption is modulated and where important additions of ammonia and the titration of buffers occur. In this proposed research we will directly examine the acidification process along the inner medullary collecting duct and the various factors which affect acidification at this site. These studies are now possible because of the development of new microanalytic methods for the in vivo and in vitro measurement of pH, pCO2, total CO2 and the other components of the acidification process and our ability to perform collections along the entire length of the IMCD.